The ability to generate cytotoxic T lymphocyte responses to minor H antigens offers a potent tool for the study of self-tolerance and self-recognition. Results obtained in this system thus far have demonstrated that the Self + X T cell repertoire is highly cross-reactive for allogeneic MHC determinants, suggesting that the response to allogeneic MHC antigens is comprised of multiple Self + X specificities. It is anticipated that studies in chimeric mice will help elucidate the mechanisms of tolerance induction with the specific intent of determining whether tolerance induction is H-2 restricted.